23517-76-2Relevant articles and documents
Synthesis, Biological Evaluation and Molecular Docking Studies of 5-indolylmethylen-4-oxo-2-thioxothiazolidine Derivatives
Geronikaki, Athina,Horishny, Volodymyr,Ivanov, Marija,Kartsev, Victor,Kostic, Marina,Matiychuk, Vasyl,Papadopoulou, Theodora A.,Petrou, Anthi,Pogodin, Pavel,Poroikov, Vladimir,Sokovic, Marina,Vizirianakis, Ioannis S.
, (2022/02/11)
Background: Infectious diseases represent a significant global strain on public health se-curity and impact on socio-economic stability all over the world. The increasing resistance to the current antimicrobial treatment has resulted in the crucial need for the discovery and development of novel entities for the infectious treatment with different modes of action that could target both sensitive and resistant strains. Methods: Compounds were synthesized using the classical organic chemistry methods. Prediction of biological activity spectra was carried out using PASS and PASS-based web applications. Pharmacophore modeling in LigandScout software was used for quantitative modeling of the antibacterial activity. Antimicrobial activity was evaluated using the microdi-lution method. AutoDock 4.2 software was used to elucidate probable bacterial and fungal molecular targets of the studied compounds. Results: All compounds exhibited better antibacterial po-tency than ampicillin against all bacteria tested. Three compounds were tested against resistant strains MRSA, P.aeruginosa and E.coli and were found to be more potent than MRSA than reference drugs. All compounds demonstrated a higher degree of antifungal activity than the reference drugs bifonazole (6–17-fold) and ketoconazole (13–52-fold). Three of the most active compounds could be considered for further development of the new, more potent antimicrobial agents. Conclusion: Compounds 5b (Z)-3-(3-hydroxyphenyl)-5-((1-methyl-1H-indol-3-yl)methylene)-2-thioxothiazol-idin-4-one and 5g (Z)-3-[5-(1H-Indol-3-ylmethylene)-4-oxo-2-thioxo-thiazolidin-3-yl]-benzoic acid as well as 5h (Z)-3-(5-((5-methoxy-1H-indol-3-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)ben-zoic acid can be considered as lead compounds for further development of more potent and safe antibacterial and antifungal agents.
Design, synthesis and biological evaluation of 3-substituted 2,5-dimethyl-N-(3-(1H-tetrazol-5-yl)phenyl)pyrroles as novel potential HIV-1 gp41 inhibitors
He, Xiao-Yang,Zou, Peng,Qiu, Jiayin,Hou, Ling,Jiang, Shibo,Liu, Shuwen,Xie, Lan
experimental part, p. 6726 - 6734 (2011/12/04)
Based on the structure of HIV-1 gp41 binding site for small-molecule inhibitors, optimization of lead 2 resulted in the discovery of a new series of 2,5-dimethyl-3-(5-(N-phenylrhodaninyl)methylene)-N-(3-(1H-tetrazol-5-yl)phenyl) pyrrole compounds with improved anti-HIV-1 activity. The most active compounds 13a and 13j exhibited significant potency against gp41 6-HB formation with IC50 values of 4.4 and 4.6 μM and against HIV-1 replication in the MT-2 cells with EC50 values of 3.2 and 2.2 μM, respectively, thus providing a new starting point to develop highly potent small-molecule HIV fusion inhibitors targeting gp41.
